Curr. Drug Metab. [JOURNAL]
Sun
200 papers
Pharmacological Complexities of Herbal Medicinal Extracts: A Review of Bioavaila-bility, Interactions, and Standardization.
Madanahalli Ramesh M, Dinesh S, Hardur Venkatappa A … +1 more , Lobo R
Curr Drug Metab · 2026 Mar · PMID 41863116 · Publisher ↗
Herbal medicines have gained remarkable popularity due to their natural origins and potential medicinal value. Nevertheless, they are chemically complex and pose signifi-cant pharmacological challenges. This review focus...
Herbal medicines have gained remarkable popularity due to their natural origins and potential medicinal value. Nevertheless, they are chemically complex and pose signifi-cant pharmacological challenges. This review focuses on the key aspects influencing their clinical use: their variable bioavailability, complex pharmacokinetics (ADME), and potential for interactions. A primary concern is herb-drug interactions, with special emphasis on the modulation of drug-metabolizing enzymes by specific phytoconstituents, which can alter drug concentrations to an extent that may be life-threatening, causing either increased toxicity or therapeutic failure. The pharmacological profile is further complicated by the complex effects of constituents, such as synergistic or antagonistic actions, which make predicting therapeutic response and safety difficult. A critical challenge in this field is the frequent dis-connect between in vitro findings and in vivo outcomes, underscoring the importance of phar-macokinetic data, particularly bioavailability, for accurate clinical risk assessment. Safety is a paramount concern, as it is often compromised by inconsistent standardization and quality control, leading to batch-to-batch variability, potential adulteration, and contamination. The absence of stringent regulation impairs therapeutic consistency and introduces health risks. To address these issues, advanced approaches are being employed to improve bioavailability, including novel drug delivery systems that enhance solubility and stability. This review em-phasizes that a rigorous, phytoconstituent-centric approach is essential for navigating the complexities of herbal medicine. By addressing challenges in pharmacokinetics, interactions, safety, standardization, and bioavailability through rigorous scientific investigation and em-bracing future perspectives, such as in silico modeling and improved regulatory frameworks, the quality, safety, and effectiveness of herbal treatments can be ensured, supporting their responsible integration into modern, evidence-based medical systems.
Lymphatic Drug Delivery System and Lipid-based Nanoformulations: Savior to Save for Patients Receiving Highly Hepatotoxic Drugs.
Vishwakarma VK, Upadhyay PK, Dubey N … +2 more , Singh A, Yadav HN
Curr Drug Metab · 2026 Mar · PMID 41863115 · Publisher ↗
The liver plays a vital role in regulating normal physiological processes in the body. Liver dysfunction can lead to mild to severe pathological conditions and, in some cases, death. To date, more than 900 drugs, toxins,...
The liver plays a vital role in regulating normal physiological processes in the body. Liver dysfunction can lead to mild to severe pathological conditions and, in some cases, death. To date, more than 900 drugs, toxins, and herbs have been identified with the potential to cause various liver diseases, including acute liver damage, cholestatic jaundice, hepatic granulomas, active chronic hepatitis, and hepatic tumors. A wide range of liver dysfunction results from drug consumption and is referred to as drug-induced liver injury (DILI). DILI significantly contributes to the immediate withdrawal of drugs from the mar-ket. Due to its numerous advantages, the oral route has long been the preferred method of drug administration, although these medicines increase the risk of liver damage. Novel drug delivery approaches, such as the lymphatic drug delivery system and lipid-based nanofor-mulations-including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers-can bypass the liver, reducing the toxic effects of various drugs. Therefore, SLNs represent a promising strategy for lymphatic drug delivery, particularly for hepatocompromised pa-tients and those taking hepatotoxic drugs. This review summarizes how lymphatic drug delivery systems and lipid-based nanoformulations can benefit hepatocompromised pa-tients and individuals on hepatotoxic medications.
Zebrafish as a Model Organism to Study Neurotoxicity: A Potential Tool for Neuroprotective Drug Discovery.
Kumar R, Dhiman P, Singh D
Curr Drug Metab · 2026 Mar · PMID 41832725 · Publisher ↗
INTRODUCTION: Danio rerio, the zebrafish, serves as an excellent model in neuroprotective drug discovery due to its conserved nervous system organization, neurotransmitter pathways, antioxidant de-fenses, and genomic sim...
INTRODUCTION: Danio rerio, the zebrafish, serves as an excellent model in neuroprotective drug discovery due to its conserved nervous system organization, neurotransmitter pathways, antioxidant de-fenses, and genomic similarity to mammals. METHODS: A systematic literature search following PRISMA 2020 guidelines was conducted across Pub-Med, Scopus, Web of Science, and Google Scholar. Studies published between 2020 and 2025 were pri-oritized, with earlier key papers included for context. The data on larval, adult, and genetically modified zebrafish models were analyzed for neurotoxic effects, focusing on study design, toxicants, and neurobe-havioral or molecular outcomes. RESULTS: Neurotoxicants such as chlorpyrifos, bisphenol, triphenyl phosphate, aluminum, ammonium ac-etate, arsenic, zinc, acrylamide, methylmercury, and tris (1,3-dichloro-2-propyl) phosphate were shown to cross the zebrafish blood-brain barrier. These exposures caused significant behavioral alterations, neu-rotransmitter imbalances, oxidative stress, and gene or protein expression changes related to brain func-tion. Analysis of the transgenic zebrafish revealed notable alterations in neuronal development and axonal morphology upon exposure to various neurotoxic chemicals. DISCUSSION: Zebrafish display neurotoxic responses with a close resemblance to mammals, supporting their translational value in neurotoxicity and drug discovery studies. However, limitations such as a less complex brain compared to mammals, quick neuronal regeneration, limited tissue access, and difficulties in drug absorption quantification warrant refinements in zebrafish models. CONCLUSION: Zebrafish offer a versatile, cost-effective, and genetically tractable system for neurotoxicity and neuroprotection research. This systematic review highlights their crucial role in neuroprotective drug discovery while emphasizing the need for improved methodological approaches to enhance translational reliability.
Advances in Carbon Nanotubes: Revolutionizing Cancer Diagnosis and Targeted Therapy.
Veer B, Prajapati S, Yadav S
Curr Drug Metab · 2026 Mar · PMID 41830119 · Publisher ↗
Nanotechnology has been applied to the diagnostic and therapeutic treatment of cancer, with Carbon Nanotubes (CNTs) serving as an effective platform for these processes. In addition to their known physicochemical charact...
Nanotechnology has been applied to the diagnostic and therapeutic treatment of cancer, with Carbon Nanotubes (CNTs) serving as an effective platform for these processes. In addition to their known physicochemical characteristics, such as high surface area, mechanical strength, and ease of functionali-zation, CNTs possess pharmacokinetic properties that enable their use in targeted drug-delivery and diag-nostic systems. Through functionalization, biodistribution, cellular uptake, and circulatory time can be modulated, thereby overcoming the limitations of traditional therapies, such as low bioavailability and systemic toxicity, and enabling more robust absorption, distribution, metabolism, and excretion profiles. Targeted CNT formulations can reduce off-target exposure and improve therapeutic efficiency through targeted delivery and controlled release. Besides, conjugation of CNTs to imaging or diagnostic agents enables improved assessment of biodistribution and metabolic characteristics, which justify their use as theranostic platforms. This review describes the new developments in CNT-based drug delivery systems for cancer treatment, with particular regard to their interactions with metabolism and the importance of these interactions on drug excretion. The fact that CNTs cross biological barriers and can boost drug bio- availability highlights the importance of these nanoparticles in enhancing the effectiveness of treatment procedures and minimizing toxicity. However, safety issues, including toxicity, long-term safety, and bi- ocompatibility, are also significant impediments to clinical translation. There will be a need to address such issues by systematizing pharmacokinetic and metabolic studies to assist in developing CNT-based solutions for precision oncology.
Mechanistic Potentials of Natural Herbal Medicines (NHMs) in Promoting Bone Regeneration: A Comprehensive Review.
Ahirwar VP, Singhai H, Thakur GS … +2 more , Rathee S, Patil UK
Curr Drug Metab · 2026 · PMID 41716052 · Publisher ↗
Bone healing remains a major clinical challenge, especially in conditions such as osteoporosis, delayed unions, and critical-sized defects, where conventional therapies often prove inadequate. Current approaches, includi...
Bone healing remains a major clinical challenge, especially in conditions such as osteoporosis, delayed unions, and critical-sized defects, where conventional therapies often prove inadequate. Current approaches, including growth factor therapies, autografts, and allografts, are limited by complications such as immunological reactions, donor-site morbidity, high cost, and poor long-term outcomes. In recent years, Natural Herbal Medicines (NHMs) have emerged as promising alternatives owing to their osteogenic, antioxidant, and anti-inflammatory properties. Phytoconstituents such as flavonoids, saponins, polyphenols, alkaloids, and minerals exert significant regulatory effects on key signaling pathways, including BMP/Smad, Wnt/β-catenin, MAPK, and RANK/RANKL/OPG, thereby restoring bone microarchitecture, suppressing osteoclastogenesis, and promoting osteoblast differentiation and mineralization. This review focuses on five medicinal plants with strong evidence in bone regeneration: Cissus quadrangularis, Dalbergia sissoo, Moringa oleifera, Withania somnifera, and Terminalia arjuna. Preclinical and clinical studies demonstrate their ability to enhance bone mineral density, collagen deposition, angiogenesis, and callus formation, while reducing oxidative stress and inflammation. Furthermore, synergistic effects have been reported in polyherbal formulations, and recent advances in biomaterials and nanotechnology-based carriers, such as scaffolds, hydrogels, and nanoparticles, offer targeted and sustained delivery, thereby improving therapeutic efficacy. Despite these promising findings, major barriers remain, including poor solubility, variability in phytochemical composition, lack of standardization, and limited large-scale clinical trials. Future research must integrate toxicological profiling, pharmacokinetic studies, and regulatory harmonization to ensure safe and effective translation of these therapies. Overall, NHMs represent an affordable, biocompatible, and culturally relevant adjunct or alternative to conventional bone-healing strategies, with the potential to revolutionize orthopedic regeneration when integrated with modern delivery platforms.
Comparative Proteomics of Hepatocytes And Hepatic Cell Lines Using Swath-MS Reveals Significant Variations In Proteins Involved In Energy, Lipid, And Xenobiotic Metabolism.
Saravanakumar A, Jamwal R, Barlock BB … +2 more , Bush X, Akhlaghi F
Curr Drug Metab · 2026 · PMID 41588973 · Publisher ↗
INTRODUCTION: Human hepatic carcinoma cell lines are widely used in vitro to study lipid and xenobiotic metabolism, as well as glucose regulation in both normal and diseased states. However, their validity is often quest...
INTRODUCTION: Human hepatic carcinoma cell lines are widely used in vitro to study lipid and xenobiotic metabolism, as well as glucose regulation in both normal and diseased states. However, their validity is often questioned due to variability in protein expression compared to primary human hepatocytes (cHH). This study aimed to quantify protein abundance in various hepatic cell lines versus cHH and human liver tissue homogenate (HLT) using a data-independent acquisition-based total protein approach (DIA-TPA). We compared the global proteome from the whole cell homogenates of HepaRG, HepG2, and Huh7 cell lines with that of cHH and HLT. METHODS: Proteins in whole cell homogenates were digested in solution using pressure-cycling technology (PCT). DIA was performed via sequential window acquisition of theoretical mass spectra (SWATH-MS), and MS2 spectra were quantified using Spectronaut™, followed by analysis with TPA. RESULTS: We identified 2715, 2578, 2874, 2717, and 3083 proteins in HepaRG, HepG2, Huh7, cHH, and HLT, respectively, at a 1% FDR. The global proteome of cHH significantly differed from that of the cancer hepatic cell lines. Among the cell lines, the global and ADME protein profile of HepaRG most closely correlated with cHH, with 89 out of 101 ADME proteins identified. Clinically relevant DMEs from the CYP450 family (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and the UGT family (UGT1A1, UGT1A3, UGT1A6, UGT2B7, and UGT2B15) were quantifiable in human hepatocytes, human liver tissue, and the HepaRG cell line. The Huh7 cell line exhibited a higher abundance of proteins related to gluconeogenesis and glycolysis compared to other groups. CONCLUSION: This study highlights the potential of untargeted global proteomics in detecting differences in protein expression among various hepatic cell lines and provides a comprehensive database to inform the choice of the cell line in future studies.
Computational Chemistry Approach in the Assessment of Potential Acyl Glucuronide-Mediated Toxicity.
Ricke ND, Walles M, Jones R … +2 more , Davis J, Gunduz M
Curr Drug Metab · 2026 Jan · PMID 41588972 · Publisher ↗
INTRODUCTION: Acyl glucuronides are common phase II metabolites of xenobiotics and can sometimes contribute to idiosyncratic toxicities. Their reactivity is primarily mediated through acyl migration and/or nucleophilic d...
INTRODUCTION: Acyl glucuronides are common phase II metabolites of xenobiotics and can sometimes contribute to idiosyncratic toxicities. Their reactivity is primarily mediated through acyl migration and/or nucleophilic displacement, and shorter acyl glucuronide half-lives are associated with increased reactivity. This reactivity can lead to metabolite-induced toxicity, posing a significant risk during drug development. METHODS: We developed regression models trained on features derived from Density Functional Theory (DFT) calculations to predict the half-lives of acyl glucuronide metabolites. The aim was to provide a computational tool to guide the design of drug candidates with more stable acyl glucuronide metabolites. RESULTS: The best-performing model achieved a strong correlation between predicted and experimental half-lives, with an R² of 0.67 on the test set. Predicted half-lives for drugs classified as clinically safe were longer than those for drugs in the warning and withdrawn categories, demonstrating a separation comparable to experimentally measured half-lives. DISCUSSION: The model is sufficiently accurate to support the optimization of acyl glucuronides for longer half-lives. Further analysis indicated that acyl glucuronide stability can be modulated by electron-donating and electron-withdrawing groups, effects that are effectively captured by the model. CONCLUSION: This modeling approach can be applied during drug discovery to reduce the risk of metabolite-related toxicity by enabling in silico screening of compound modifications and ranking them based on predicted effects on acyl glucuronide half-life.
Exploring Microbiome-Based Therapy: Bacterial Flavonoid Synthesis as a Novel Approach to PCOS Treatment.
Goyal N, Sharma S, Bhatia R … +1 more , Gupta S
Curr Drug Metab · 2026 Jan · PMID 41588971 · Publisher ↗
BACKGROUND: PCOS is a common endocrine disorder characterized by metabolic irregularities, hormonal imbalance, and ovarian dysfunction. Traditional therapies, including dietary changes, herbal remedies, and lifestyle mod...
BACKGROUND: PCOS is a common endocrine disorder characterized by metabolic irregularities, hormonal imbalance, and ovarian dysfunction. Traditional therapies, including dietary changes, herbal remedies, and lifestyle modifications, offer limited efficacy in addressing the complex pathophysiology of PCOS. METHOD: A literature review was conducted using PubMed, Google Scholar, and ScienceDirect to identify studies on gut microbiota and microbiome-based management strategies for PCOS. RESULT: Emerging evidence highlights the role of gut bacteria in regulating hormonal and metabolic functions, sparking interest in microbiota-targeted therapies. Microbial flavonoid synthesis by species such as Streptomyces and Escherichia coli may positively influence endocrine and metabolic pathways relevant to PCOS. DISCUSSION: Modulating the gut microbiome, particularly through microbial flavonoid production, represents a promising therapeutic avenue. However, most evidence remains pre-clinical, with limited clinical validation. Key gaps include mechanistic understanding, safety evaluation, and translational research. Integrating microbiome-targeted interventions with conventional therapies could enhance metabolic and hormonal regulation, offering improved outcomes for women with PCOS. CONCLUSION: Microbiome-based medicinal approaches, including microbial flavonoid production, may offer novel strategies for PCOS management. Rigorous preclinical studies and well-designed clinical trials are essential to establish their efficacy, safety, and therapeutic potential.
The Multifaceted Role of Cytochrome P450 Isoenzymes in Alcoholic and Metabolic (Dysfunction) Fatty Liver Diseases.
Qinna NA, Estatieh ON, Ghanim BY
Curr Drug Metab · 2026 · PMID 41588970 · Publisher ↗
The current review explores the alterations in cytochrome P450 (CYP) activity and expression during alcoholic liver disease (ALD) and metabolic (dysfunction)-associated fatty liver disease (MAFLD), formerly known as non-...
The current review explores the alterations in cytochrome P450 (CYP) activity and expression during alcoholic liver disease (ALD) and metabolic (dysfunction)-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD). CYP is a major family of enzymes involved in the metabolism of numerous endogenous and exogenous compounds. Thus, any change in CYP activity or expression could disrupt metabolic pathways. Alterations in hepatic CYP have been shown to contribute to the development of ALD and MAFLD, and vice versa. CYP isoforms also participate in fatty acid metabolism and are involved in fatty liver development in ALD and MAFLD by regulating various cell signaling pathways and transcription factors. Several mechanisms by which CYP causes oxidative stress and liver injury are reviewed here. Additionally, CYP isoforms are known to break down cholesterol into bile acids, which play a role in lipid absorption in the small intestine and modulate the bile acid pool. This review discusses the role of CYP isoforms in the progression of ALD and MAFLD, as understanding these mechanisms can help identify potential targets for the prevention and treatment of both diseases.
Therapeutic Implications of Nutraceutical Nanotechnology for the Treatment of Chronic Diseases.
Adhikari B, Venkatesh DN, Puri V … +1 more , Sharma A
Curr Drug Metab · 2026 Jan · PMID 41510732 · Publisher ↗
Nanotechnology possesses therapeutic value in managing chronic disease, but it has limitations like as solubility, stability, and targeted delivery in clinical applications. The review explores how nanotechnology-based d...
Nanotechnology possesses therapeutic value in managing chronic disease, but it has limitations like as solubility, stability, and targeted delivery in clinical applications. The review explores how nanotechnology-based delivery systems improve the efficacy, bioavailability, and targeted actions of nutraceutical compounds. Health benefits, sustainable nanotechnology, market size, and growth forecasts have shown positive results in this industry over the last two decades. The disease-like respiratory, diabetes, Alzheimer's and Parkinson's, and breast cancer top focused sectors for this nutraceuticals sector. Most literature has been collected from 2020-2025 using PubMed, Scopus, Google Scholar, and Web of Science. The different criteria included preclinical, clinical, and nanotechnology-integrated nutraceutical studies. The liposomes, dendrimers, nanoemulsions, and polymeric nanoparticles significantly enhance the stability and delivery of key bioactive as example like curcumin, resveratrol, and omega-3. Early-stage clinical trials show promise for diseases like Alzheimer's, diabetes, and cancer. Nanotechnology is the reshaping of nutraceutical therapy, through regulatory, toxicology, and large-scale validation gaps persist. Future work must focus on green synthesis, long-term safety, and harmonized approval pathways. Despite this, the industry still needs collaboration between academic researchers, scientists, and regulatory bodies to start the next generation of clinical trials and treatments that can reduce the risk of diseases and death in the future.
Development and Characterization of Ricinoleic Acid-Loaded Chitosan Nanoparticles for Targeted Hepatoprotective Drug Delivery.
Sarthi S, Bhardwaj H, Jangde RK
Curr Drug Metab · 2026 · PMID 41487008 · Publisher ↗
INTRODUCTION: Ricinoleic acid (RA), a fatty acid derived from castor oil (Ricinus communis), exhibits potent antioxidant activity and hepatoprotective properties, primarily attributed to its ability to mitigate oxidative...
INTRODUCTION: Ricinoleic acid (RA), a fatty acid derived from castor oil (Ricinus communis), exhibits potent antioxidant activity and hepatoprotective properties, primarily attributed to its ability to mitigate oxidative stress. However, its therapeutic application is limited by poor bioavailability due to high metabolism, low intestinal permeability, poor water solubility, rapid urinary and biliary elimination, frequent dosing requirements, and a short half-life. This study aimed to optimize the formulation of ricinoleic acid-loaded chitosan nanoparticles (RA-CSNPs) for improved delivery and bioavailability using the ionic gelation technique. METHOD: The formulation was developed using chitosan as the polymer and sodium tripolyphosphate (STPP) as the cross-linking agent. The synthesized nanoparticles were characterized for particle size (PS: 164.15 nm), polydispersity index (PDI: 0.259), zeta potential (ZP: +30.25 mV), and entrapment efficiency (EE: 97.07%) and drug release within 24 hours. Structural and thermal properties were assessed using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). RESULTS: The in vitro drug release profile of the RA-CSNPs showed a cumulative release of 92.12%, demonstrating significant controlled release. Additionally, the antioxidant activity was measured at 84.45%, indicating that RA retained its bioactivity in the nanoparticle formulation. DISCUSSION: These results highlight the potential of RA-CSNPs as an effective drug-delivery system to overcome the bioavailability challenges of ricinoleic acid. The controlled release and antioxidant activity of the formulation are promising for therapeutic applications in various oxidative stress-related diseases. However, limitations in scaling up nanoparticle production and conducting long-term pharmacokinetic studies need to be addressed in future research. CONCLUSION: This study successfully demonstrates the potential of RA-loaded chitosan nanoparticles as a novel and efficient drug delivery system. The formulation provides controlled release, enhancing the bioavailability of ricinoleic acid and offering a promising strategy for improving its therapeutic efficacy in clinical applications.
A Systematic Review of Pharmacokinetic Models of Vancomycin in Adult Patients (2020-2024): Trends, Variability, and Key Covariates.
Fresquet-Molina R, Allende-Bandres MLÁ, Arenere-Mendoza M … +7 more , Sopena-Carrera L, Navarro-Pardo I, Jimeno-Martin Á, Salvador-Gomez T, Gomez-Barrera M, Sáez-Benito-Suescun L, Berenguer-Torrijo N
Curr Drug Metab · 2025 Nov · PMID 41255361 · Full text
INTRODUCTION: This systematic review aimed to identify, evaluate, and critically an-alyze pharmacokinetic models of vancomycin in adult populations published in PubMed and EMBASE between 2020 and 2024. MATERIALS AND METH...
INTRODUCTION: This systematic review aimed to identify, evaluate, and critically an-alyze pharmacokinetic models of vancomycin in adult populations published in PubMed and EMBASE between 2020 and 2024. MATERIALS AND METHODS: Twenty-two studies were included, describing 24 models character-ized by substantial heterogeneity in terms of study populations, methodological design, and covariate selection. Most models were developed in Asia and focused on hospitalized patients, particularly those in intensive care units (ICUs). Data from 2150 patients were analyzed, with an average of 93 patients per model. RESULTS: The models demonstrated high variability in pharmacokinetic parameters, such as vancomycin clearance (Cl) and volume of distribution (Vd), influenced by factors, such as renal function, weight, age, and comorbidities. The meta-analysis conducted on clearance and interindividual variability in clearance (IIV Cl) revealed high heterogeneity among the ana-lyzed studies. The average vancomycin clearance was 4.23 L/h, with higher values observed in neurosurgical, oncohematologic patients, and those with increased renal function. The vol-ume of distribution showed greater variability in obese patients and those undergoing continu-ous renal replacement therapy. Creatinine clearance (ClCr) was identified as a significant co-variate in 66% of the models, while weight was significant in 33%. Other important covariates included age, sex, serum creatinine, serum urea, and the hospital admission unit. The meta-analysis of Cl and IIV Cl showed high heterogeneity among the studies, with I² values of 0.83 for Cl and 0.98 for IIV Cl, indicating substantial variability. DISCUSSION: The limitations of this study included the diversity of the analyzed populations, which made it challenging to assess the model's suitability. While the models showed advances in precision, challenges, such as the lack of external validation and discrepancies in dosing recommendations, remain. CONCLUSION: This review paper has highlighted the need to validate models in diverse popula-tions and clinical settings to optimize personalized vancomycin therapy in adults. The findings have highlighted the importance of validating or adapting pharmacokinetic models to the spe-cific characteristics of each hospital population.
Molecular Pathways Involved in Drug-Induced Hepatotoxicity: A Mini Review.
Bhati A, Mazumder A, Bansal P … +1 more , Salahuddin
Curr Drug Metab · 2025 Nov · PMID 41239931 · Publisher ↗
Drug-induced hepatotoxicity (DIH) poses a significant clinical challenge due to its unpredicta-ble nature and diverse manifestations. The liver, with its central role in metabolism and close association with the gastroin...
Drug-induced hepatotoxicity (DIH) poses a significant clinical challenge due to its unpredicta-ble nature and diverse manifestations. The liver, with its central role in metabolism and close association with the gastrointestinal tract, is particularly susceptible to drug-induced toxicity. DIH encompasses a spectrum of liver injuries, including hepatocellular, cholestatic, and mixed patterns, which may increase the risk of other liver diseases. This review examines diverse examples and molecular mechanisms under-lying DIH, highlighting the influence of genetic predisposition, drug interactions, and pre-existing liver conditions. Given the complexity and variability of hepatotoxic responses to numerous medications, un-derstanding these mechanisms is crucial for improving the diagnosis and management of DIH.
Lung-Targeting Cepharanthine Polymer Micelles Modified with Mannose: Effectiveness Against Acute Lung Injury Evaluated Using in vitro and in vivo Analyses.
Xue R, Chen YY, Mei JH … +7 more , Zhang PP, Jin WB, Cui LL, Zhao XY, Zhang HL, Luo LQ, Ma YS
Curr Drug Metab · 2025 Nov · PMID 41220259 · Publisher ↗
<p>Introduction: The currently available therapies for acute lung injury (ALI), including gluco-corticoids, protease inhibitors, and heparin, have limited clinical efficacy and are often associated with significant side...
<p>Introduction: The currently available therapies for acute lung injury (ALI), including gluco-corticoids, protease inhibitors, and heparin, have limited clinical efficacy and are often associated with significant side effects. Cepharanthine (CEP) has demonstrated effectiveness in treating pulmonary dis-eases, but its clinical application is restricted by low solubility and poor bioavailability. This study aimed to develop mannosylated cepharanthine-loaded polymeric micelles (MA-CEP-PMs) to improve CEP bio-availability and enhance lung-targeted delivery for the treatment of ALI. </p><p> Methods: The pharmacokinetics of MA-CEP-PMs in rats were assessed using Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). Lung-targeting ability was evaluated through tissue distribution studies and near-infrared imaging. In a rat model of ALI induced by lipopolysaccharide (LPS), anti-ALI effects were assessed via general physiological indicators, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot analysis. Hematoxylin-eosin (HE) staining was used to examine hepatotoxicity and nephrotoxicity of MA-CEP-PMs in normal rats. Cyto-toxicity of the mannosylated polyethylene glycol-poly(lactic-co-glycolic acid) copolymer (MA-PEG-PLGA) on NR8383 cells was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake experiments were performed to determine the targeting ability of MA-PEG-PLGA in NR8383 cells, and the effects of MA-CEP-PMs on inflammatory cytokines were analyzed using ELISA.</p><p> Results: MA-CEP-PMs significantly increased the AUC and exhibited better lung targeting ability com-pared to the unmodified micelles (P < 0.01). In the ALI model, MA-CEP-PMs improved the thymus and spleen indices, decreased the lung wet-to-dry weight ratio (P < 0.05), alleviated model animal damage, and inhibited inflammatory factor and nuclear factor-κB (NF-κB)-related protein levels (P < 0.05). MA-CEP-PMs exhibited no significant hepatotoxicity or nephrotoxicity. MA-PEG-PLGA exhibited low tox-icity against NR8383 cells and greater cell uptake, indicating stronger targeting of the lung. MA-CEP-PMs also exhibited more potent anti-inflammatory effects.</p><p> Discussion: This study focused on the short-term therapeutic effects of ALI, whereas the clinical man-agement of lung injury often requires long-term intervention. Future research should therefore assess the long-term efficacy of this delivery system in chronic lung injury, along with determining its safety profile and potential impacts on extra-pulmonary organs. While the involvement of the NF-κB pathway in the anti-inflammatory effects has been confirmed, it remains to be deciphered whether mannose modification synergistically regulates other signaling pathways and what the specific intracellular targets of CEP are, which would require further exploration through detailed molecular biology experiments.</p><p> Conclusion: The MA-CEP-PMs significantly improved CEP bioavailability and increased lung targeting. They exhibited good safety and had a significant effect on ALI management.</p>.
Applications of Proteomics, Glycomics, and Metabolomics Analyses in Systemic Lupus Erythematosus.
Xu R, Zhang G, Wang S … +2 more , Yang T, Wang C
Curr Drug Metab · 2025 Nov · PMID 41193451 · Publisher ↗
Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disorder in-fluenced by genetic predisposition, immune dysregulation, environmental triggers, and epi-genetic modifications. Despite advances in treatment...
Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disorder in-fluenced by genetic predisposition, immune dysregulation, environmental triggers, and epi-genetic modifications. Despite advances in treatment, many patients experience recurrent symptoms and adverse effects. Recent large-scale studies have revealed significant alterations in proteins, glycopeptides, and metabolites in SLE, deepening our understanding of its path-ogenesis. Emerging omics technologies, such as proteomics, glycomics, and metabolomics, enable the high-throughput identification of disease-related biomarkers. However, biological processes are typically driven by the interplay among multiple molecular layers. Therefore, integrative multi-omics approaches have become essential for uncovering potential bi-omarkers and risk factors. This review summarizes the classification of SLE biomarkers and recent advances in diagnostic applications across proteomics, glycomics, and metabolomics, aiming to support the development of more precise diagnostic strategies for SLE.
Smart Stimuli-Responsive Drug Delivery Systems for Advanced Diabetes Management.
Jaiswal KP, Monika, Mazumder R … +1 more , Mazumder A
Curr Drug Metab · 2025 · PMID 41193450 · Publisher ↗
Traditional treatment methods for the management of diabetes, such as oral hypoglycemic medications and insulin injections, include drawbacks like systemic adverse effects, inconsistent medication levels, and low complia...
Traditional treatment methods for the management of diabetes, such as oral hypoglycemic medications and insulin injections, include drawbacks like systemic adverse effects, inconsistent medication levels, and low compliance. To avoid difficulties, glycemic levels in diabetic patients, a long-term metabolic condition, must be precisely and consistently controlled. Smart therapeutic systems allow for precise, on-demand medication release in response to local physiological or environmental cues, such as glucose levels, pH, temperature, or enzyme activity. They provide a possible substitute for conventional diabetic therapies. As these systems only administer medications when and where needed, they reduce side effects while simultaneously increasing therapeutic efficacy and patient compliance. These systems are designed to respond to signals from external sources (such as light, ultrasound, or magnetic fields) or stimuli like temperature, pH, glucose levels, and enzymes. As they use glucose-sensitive substances like phenylboronic acid, glucose oxidase, or polymers to precisely release insulin in hyperglycemic circumstances, glucose-responsive delivery methods are essential for diabetes. This review discusses a stimuli-responsive drug delivery system designed for diabetes treatment, with a focus on the developments in biomaterials, nanotechnology, and engineering that improve its effectiveness and biocompatibility. Along with the possibility of combining a stimuli-responsive drug delivery system with wearable technology for continuous glucose monitoring and intelligent insulin delivery, issues, such as manufacturing complexity, stability, and patient safety, are also addressed. The stimuli-responsive drug delivery system has the potential to revolutionize diabetes management by bridging the gap between physiological needs and therapeutic delivery, providing better glucose control, fewer side effects, and an enhanced standard of living for patients.
A Lack of Studies on the Metabolism and Disposition of Hot Compound Class: Triphenylphosphonium-Conjugated Compounds.
Hu M, Chen J
Curr Drug Metab · 2025 Nov · PMID 41185510 · Publisher ↗
Abstract loading — click title to view on PubMed.
Study on the Mechanism of Anti-Cerebral Ischemia-Reperfusion Injury of Ai Pian Based on Network Pharmacology and Metabolomics.
Lian J, Ma Y, Lu D … +3 more , Wang P, Zhang M, Dong T
Curr Drug Metab · 2025 Oct · PMID 41178775 · Full text
OBJECTIVE: The objective of this study was to investigate the mechanism of anti-cerebral ischemia-reperfusion injury (anti-CIRI) of Ai pian by using the network pharmacology approach combined with serum metabolomics tech...
OBJECTIVE: The objective of this study was to investigate the mechanism of anti-cerebral ischemia-reperfusion injury (anti-CIRI) of Ai pian by using the network pharmacology approach combined with serum metabolomics technique based on UPLC-MS. METHODS: The cerebral ischemia-reperfusion injury (CIRI) model was established by middle cerebral artery occlusion (MCAO). The therapeutic effect of Ai pian on CIRI rats was evaluated by behavioral test, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, and hematoxylin-eosin (HE) staining. The active compound-potential target-disease network for Ai Pian in the treatment of CIRI was established using network pharmacology methods. Rat serum was detected by the metabolomics technique based on UPLC-MS. A Western blot was used to validate common targets of the network pharmacology approach combined with serum metabolomics. RESULTS: The process of treating CIRI with Ai Pian involved regulating enzyme, nuclear receptor, and transcription factor activity, managing the inflammatory response, and participating in biofilm composition. Twenty endogenous potential biomarkers were screened and submitted to MetaboAnalyst 6.0 for pathway and enrichment analysis. Four metabolic pathways were identified: butanoate metabolism, fructose and mannose metabolism, alanine, aspartate, and glutamate metabolism, and pyrimidine metabolism. Fructose and mannose metabolism and pyrimidine metabolism were two key pathways. Western blot analysis suggested that DHODH, TYMS, and AKR1B1 may be targets through which therapeutic effects are exerted. CONCLUSION: This research contributed to the development of Ai pian as an adjunctive drug for treating CIRI and provided a basis for further research on CIRI.
A Population Pharmacokinetics Model of Busulfan in Pediatric Patients with Thalassemia Major.
Lai F, Cui D, Li Y … +7 more , Liu S, Chen Z, Su Q, Xiang S, Feng X, Yao F, Li X
Curr Drug Metab · 2025 · PMID 41116280 · Publisher ↗
PURPOSE: This research aimed to establish a population pharmacokinetic (PPK) model for busulfan (Bu) in Chinese pediatric patients with thalassemia major. We analyzed pharmacokinetic (PK) parameter variability and explor...
PURPOSE: This research aimed to establish a population pharmacokinetic (PPK) model for busulfan (Bu) in Chinese pediatric patients with thalassemia major. We analyzed pharmacokinetic (PK) parameter variability and explored potential covariates affecting Bu disposition using patient data. These findings are intended to support the optimization and personalization of Bu dosage regimens for children with thalassemia major. METHODS: Concentration-time samples were collected retrospectively from 62 pediatric patients with thalassemia major. These patients had previously received intravenous Bu as a preparatory regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT). A PPK model of Bu was developed through nonlinear mixed-effects modeling. This modeling process, conducted using NONMEM software, concurrently involved data analysis and examination of the effect of covariates on Bu pharmacokinetics. For validation purposes, the resulting model was evaluated against an external dataset consisting of 20 individuals. RESULTS: The pharmacokinetic results were optimally analyzed using a model that incorporated a onecompartment model with first-order elimination. Body surface area (BSA) was subsequently identified as the most significant factor influencing both Bu clearance (CL) and volume of distribution (V). Diagnostic evaluations, encompassing goodness-of-fit plots, normalized prediction distribution errors, and visual predictive checks, confirmed the satisfactory fit and predictability of the final PPK model. Moreover, prediction- based diagnostic indices (MDPE%, 15.75; MAPE%, 22.26; F20%, 45.71; and F30%, 58.57) from external validation showed that no significant bias was detected when comparing the model's predicted concentrations against the observed data. CONCLUSION: The present study developed the first PPK model characterizing the pharmacokinetics of Bu specifically in children with thalassemia major. This study's final PPK model demonstrated that BSA was the key predictive covariate for CL and V.
Pharmacokinetics of Trelagliptin in Rats after Exposure to Acute and Chronic High Altitude Hypoxia.
Huan Z, Duo D, Zhao N … +4 more , Chang Y, Xu G, Wu X, Wang Y
Curr Drug Metab · 2025 · PMID 41116279 · Publisher ↗
BACKGROUND: As a long-acting DPP-4 inhibitor administered orally once a week, trelagliptin can address the issues of frequent medication and poor compliance associated with traditional hypoglycemic drugs. METHODS: The Hy...
BACKGROUND: As a long-acting DPP-4 inhibitor administered orally once a week, trelagliptin can address the issues of frequent medication and poor compliance associated with traditional hypoglycemic drugs. METHODS: The Hypoxia model in rats was constructed at an altitude of approximately 4300 meters. The plasma concentration of trelagliptin was determined by LC-MS/MS. The biochemical indices and the protein expression levels of P-gp and OCT2 in the kidneys of rats were determined to explain the possible reasons for the pharmacokinetic changes of trelagliptin. RESULTS: This study demonstrated that the pharmacokinetic parameters of trelagliptin were significantly changed in high-altitude hypoxic environments. Compared with the control group, the AUC, MRT, t1/2, and Vd were remarkably increased during acute and chronic hypoxia, while the CL and Ke were decreased. Additionally, the biochemical indexes and protein expression of P-gp and OCT2 were significantly altered. CONCLUSION: The study demonstrated that high-altitude hypoxia significantly altered trelagliptin's pharmacokinetics, slowing clearance, prolonging elimination half-life and residence time, and increasing bioavailability. These changes suggested that the optimal therapeutic dosage of trelagliptin should be reassessed under hypoxic exposure.
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